Psychopharmacology Considerations in Treating Patients With Rheumatological Disorders

Psychiatric disorders are common in patients with rheumatological disorders, due to primary psychiatric disorders, secondary syndromes (due to CNS involvement), or side effects of medications. The three most common rheumatological disorders are rheumatoid arthritis, osteoarthritis, and systemic lupus erythematosus.

Rheumatoid arthritis (RA) affects about 1 percent of the population, with women being affected approximately three times more frequently than men. Twenty percent of patients with RA have a psychiatric disorder, most often depression. Depressed patients with RA have more pain, poorer adherence to medication, and poorer quality of life than patients without depression.

Osteoarthritis (OA) is the most common joint disease, with the idiopathic form being the most prevalent. Secondary OA arises most frequently as the result of trauma (acute or chronic), although it also may occur in conjunction with a variety of metabolic and endocrine disorders. The prevalence of OA increases sharply with age: fewer than 2 percent of women younger than 45 years are affected, compared with 30 percent of those between 45 and 64 years of age and 68 percent of those older than 65 years. Research on depression in OA patients has revealed similar findings to those of patients with rheumatoid arthritis.

Systemic lupus erythematosus (SLE) has a prevalence of about 0.1 percent with 90 percent of cases in women, usually of childbearing age. African-American women are affected about three times as often as non-Latina white women. Thirty to 50 percent of patients with SLE have depression, 13 percent to 24 percent have anxiety, 3 percent to 4 percent have mania or mixed episodes, and up to 5 percent have psychosis. CNS involvement is a major cause of morbidity in SLE, second only to renal failure as a cause of mortality.

Less common rheumatological disorders that may present with neuropsychiatric manifestations from CNS involvement include SjɆgren’s syndrome, temporal (giant cell) arteritis, polymyositis, polyarteritis nodosa, Behçet’s syndrome, and granulomatosis with polyangiitis (Wegener’s granulomatosis).

Treatment in Rheumatoid Arthritis, Osteoarthritis

For the most part, treatment of psychiatric disorders in patients with rheumatological disease is similar to treatment of patients with other chronic medical diseases. Few randomized, controlled trials have been carried out specifically in patients with rheumatological disorders, but SSRIs, SNRIs, and TCAs have been shown effective for depression. When pharmacotherapy of depression was part of a collaborative care approach, outcomes were improved.

Although current evidence indicates that all antidepressants have roughly equal efficacy in treating depression, they differ in their analgesic efficacy, tolerability, and potential for drug interactions. TCAs have long been recognized to have analgesic benefits, even at low dose and independent of the presence of depression. Taken at bedtime, they may improve sleep in arthritis patients, but TCAs have more potential side effects than other antidepressants and are less well tolerated. Compared with TCAs, SSRIs have comparable antidepressant efficacy but less analgesic efficacy. SNRIs possess more analgesic potential than SSRIs. Most randomized, controlled trials demonstrating analgesic efficacy of antidepressants in rheumatological disorders have been of TCAs.

Treatment in Systemic Lupus Erythematosus

Psychopharmacological treatment of neuropsychiatric symptoms (particularly psychosis and mania) in patients with SLE is a challenge, with no guidance from randomized, controlled trials. High-dose corticosteroids are considered first-line treatment to suppress CNS inflammation but may exacerbate neuropsychiatric symptoms. Antipsychotics are frequently used for symptomatic treatment concurrent with corticosteroids. Patients with CNS lupus must be monitored closely for extrapyramidal symptoms and seizures. Lithium and anticonvulsants are often used for their mood-stabilizing properties. Benzodiazepines should be used with caution because of the risk of confusion and disinhibition.

Psychotropic Drug-Induced Lupus

Patients who are receiving antipsychotic drugs, particularly chlorpromazine, may have positive antinuclear and antiphospholipid antibodies, but most do not develop signs of an autoantibody-associated disease. Compared with other (nonpsychiatric) drugs known to cause a symptomatic lupus-like syndrome, chlorpromazine and carbamazepine carry low risk, and several other psychotropics (valproic acid and other anticonvulsants, phenelzine, and lithium) carry very low risk. Drug-induced lupus is actually more commonly caused by rheumatological drugs (especially infliximab and adalimumab) than psychotropics. CNS involvement is usually absent in drug-induced lupus. After discontinuation of the drug, symptoms and antibody titers decline usually over a period of weeks.

Drug-Drug Interactions

Relatively few important drug interactions occur between rheumatological and psychopharmacological agents. The most important possible interactions involve risk for increased gastrointestinal bleeding when nonsteroidal anti-inflammatory drugs are combined with serotonergic agents, particularly SSRIs, SNRIs, and tertiary-amine TCAs. The potential for synergistic myelosuppressive effects exists with the combination of immunosuppressive agents and psychotropics with this effect (for example, clozapine, carbamazepine, valproate, and mirtazapine), but this has been rarely reported. ■